2000 Fiscal Year Annual Research Report

高次生命現象の基盤となるbZip型転写因子制御ネットワークの包括的解析

Research Project

Project/Area Number	12308036
Research Institution	University of Tsukuba
Principal Investigator	山本雅之筑波大学, 基礎医学系, 教授 (50166823)
Co-Investigator(Kenkyū-buntansha)	本橋ほづみ筑波大学, 基礎医学系, 講師 (00282351)
Keywords	bZip型転写因子 / 遺伝子破壊マウス / 転写制御 / 巨核球 / 神経変性症 / 遺伝子制御ネットワーク
Research Abstract	今年度は以下の成果を得た. 1)小Maf群因子3重欠損マウスの作製:MafG,MafK,MafF全ての小Maf群因子を欠損するマウスを作製したところ,同マウスは胎生10.5日で致死であることが明らかになった.胎盤の形成異常が認められ,胎児の死因は,胎盤の機能不全であると考えられた. 2)bZipネットワークの構成因子の量的・質的変動と相互作用の解析:MafG欠損マウスでは,巨核球からの血小板放出過程であるproplatelet formation (PPF)に障害が認められる.一方,小Maf群因子を巨核球特異的に過剰発現するマウスを作製したところ,やはり,PPFが障害された.この両者を交配すると,小Maf群因子の量は野生型とほぼ同じレベルに復帰し,PPFの障害も回復した.これにより,MAREを介する転写の活性化は小Maf群因子の存在量の増減により変化することが個体レベルで示された. 3)bZIpネットワークの標的遺伝子の探索:mafG-/-:: mafK+/-マウスの巨核球のmRNAと野生型マウスのmRNAとでサブトラクションを試みた結果,アクチン,チュブリンなどの細胞骨格系の遺伝子発現が,変異マウス由来の巨核球において減少していることが明らかになった. 4)bZipネットワークを動かすシグナルの解析:mafG-/-:: mafK+/-マウスの神経細胞において,ユビキチンが蓄積していることが明らかになった.これにより,mafG-/-:: mafK+/-マウスの神経症状の発症原因は,神経細胞における異常蛋白質の蓄積である可能性が考えられた.bZipネットワークの機能を制御する刺激として,神経細胞の活動に伴う酸化ストレスが関与している可能性について,現在検討中である.

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Nishimura,S.: "A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene."Mol.Cell.Biol.. 20. 713-723 (2000)
[Publications] Pan,X.: "Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions."J.Biochem.. 127. 105-112 (2000)
[Publications] Kobayashi,A.: "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/POZ domain."Mol.Cell.Biol.. 20. 1733-1746 (2000)
[Publications] Onodera,K.: "Perinatal synthetic lethality and hematopoietic defects in compound mafG :: mafK mutant mice."EMBO J. 19. 1335-1345 (2000)
[Publications] Katsuoka,F.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J.. 19. 2980-2991 (2000)
[Publications] Ishii,T.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole."Carcinogenesis. 21. 1013-1016 (2000)
[Publications] Hoshino,H.: "Oxidative stress abolishes leptomycine B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element."J.Biol.Chem.. 275. 15370-15376 (2000)
[Publications] Ishii,T.: "Transcription factor Nrf2 coordinately regulates a group of oxidative stressinducible genes in macrophages."J.Biol.Chem.. 275. 16023-16029 (2000)
[Publications] Takahashi,S.: "GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies."Blood. 96. 910-916 (2000)
[Publications] Takahashi,S-I.: "Cloning of a coproporphyrinogen oxidase promoter regulatory element binding protein."Biochem.Biophys.Res.Commun.. 2732. 596-602 (2000)
[Publications] Hayes,J.D.: "The Nrf2 transcription factor contributes both to the basal expression of glutathion S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin."Biochem.Soc.Trans.. 28. 33-41 (2000)
[Publications] Zhou,Y.: "GATA2 is required for the generation of V2 intemeurons."Development. 127. 3829-3838 (2000)
[Publications] Toki,T.: "Functional characterization of the two alternative promoters of human p45 NF-E2 gene."Exp.Hematol.. 28. 1113-1119 (2000)
[Publications] Wakabayashi,N.: "A novel cis-acting element regulates HES-1 gene expression in P19 embryonal carcinoma cells treated with retinoic acid."J.Biochem.. 128. 1087-1095 (2000)
[Publications] Motohashi,H.,: "Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins."Cell. 103. 865-875 (2000)

2000 Fiscal Year Annual Research Report

高次生命現象の基盤となるbZip型転写因子制御ネットワークの包括的解析

Principal Investigator

山本 雅之 筑波大学, 基礎医学系, 教授 (50166823)

Research Products

[Publications] Nishimura,S.: "A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene."Mol.Cell.Biol.. 20. 713-723 (2000)

[Publications] Pan,X.: "Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions."J.Biochem.. 127. 105-112 (2000)

[Publications] Kobayashi,A.: "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/POZ domain."Mol.Cell.Biol.. 20. 1733-1746 (2000)

[Publications] Onodera,K.: "Perinatal synthetic lethality and hematopoietic defects in compound mafG :: mafK mutant mice."EMBO J. 19. 1335-1345 (2000)

[Publications] Katsuoka,F.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J.. 19. 2980-2991 (2000)

[Publications] Ishii,T.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole."Carcinogenesis. 21. 1013-1016 (2000)

[Publications] Hoshino,H.: "Oxidative stress abolishes leptomycine B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element."J.Biol.Chem.. 275. 15370-15376 (2000)

[Publications] Ishii,T.: "Transcription factor Nrf2 coordinately regulates a group of oxidative stressinducible genes in macrophages."J.Biol.Chem.. 275. 16023-16029 (2000)

[Publications] Takahashi,S.: "GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies."Blood. 96. 910-916 (2000)

[Publications] Takahashi,S-I.: "Cloning of a coproporphyrinogen oxidase promoter regulatory element binding protein."Biochem.Biophys.Res.Commun.. 2732. 596-602 (2000)

[Publications] Hayes,J.D.: "The Nrf2 transcription factor contributes both to the basal expression of glutathion S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin."Biochem.Soc.Trans.. 28. 33-41 (2000)

[Publications] Zhou,Y.: "GATA2 is required for the generation of V2 intemeurons."Development. 127. 3829-3838 (2000)

[Publications] Toki,T.: "Functional characterization of the two alternative promoters of human p45 NF-E2 gene."Exp.Hematol.. 28. 1113-1119 (2000)

[Publications] Wakabayashi,N.: "A novel cis-acting element regulates HES-1 gene expression in P19 embryonal carcinoma cells treated with retinoic acid."J.Biochem.. 128. 1087-1095 (2000)

[Publications] Motohashi,H.,: "Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins."Cell. 103. 865-875 (2000)

山本雅之筑波大学, 基礎医学系, 教授 (50166823)